Clinical Trials List
Protocol Number1245.69
NCT Number(ClinicalTrials.gov Identfier)NCT02414958
2015-09-01 - 2017-04-04
Phase III
Terminated7
ICD-10E10.9
Type 1 diabetes mellitus without complications
ICD-9250.01
Diabetes mellitus without mention of complication, Type I [insulin dependent type] [IDDM] [juvenile type], not stated as uncontrolled
A Phase III, randomised, double blind, placebo-controlled, parallel group, efficacy, safety and tolerability trial of once daily, oral doses of Empagliflozin as Adjunctive to inSulin thErapy over 52 weeks in patients with Type 1 Diabetes Mellitus (EASE2)
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Trial Applicant
Boehringer Ingelheim
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Sponsor
Boehringer Ingelheim
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 古淑如 Division of Endocrinology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Type 1 Diabetes Mellitus
Objectives
The objective of this study is to assess the efficacy, safety, tolerability and
pharmacokinetics (PK) of once daily oral doses of empagliflozin 10 mg and 25 mg
in patients with Type 1 diabetes mellitus (T1DM) as adjunctive to insulin therapy
Test Drug
Jardiance®
Active Ingredient
Empagliflozin
Dosage Form
film-coated tablet
Dosage
10 / 25
Endpoints
Primary endpoint is the change from baseline in HbA1c after 26 weeks
Key secondary endpoints are:
incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma
glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per
patient-year from week 5 to week 26
o severe hypoglycaemic AEs are defined as events requiring the
assistance of another person to actively administer carbohydrate,
glucagon or other corrective actions. Plasma glucose concentrations
may not be available during an event, but neurological recovery
following the return of plasma glucose to normal is considered
sufficient evidence that the event was induced by a low plasma
glucose concentration
incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma
glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per
patient-year from week 1 to week 26
change from baseline in body weight (kg) after 26 weeks
change from baseline in total daily insulin dose (TDID), U/kg, after 26 weeks
change from baseline in the percentage of time spent in target glucose range of
70-180 mg/dL (3.9-10.0 mmol/L) as determined by continuous glucose
monitoring (CGM) in weeks 23 to 26
change from baseline in systolic blood pressure (SBP) after 26 weeks
change from baseline in diastolic blood pressure (DBP) after 26 weeks
Key secondary endpoints are:
incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma
glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per
patient-year from week 5 to week 26
o severe hypoglycaemic AEs are defined as events requiring the
assistance of another person to actively administer carbohydrate,
glucagon or other corrective actions. Plasma glucose concentrations
may not be available during an event, but neurological recovery
following the return of plasma glucose to normal is considered
sufficient evidence that the event was induced by a low plasma
glucose concentration
incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma
glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per
patient-year from week 1 to week 26
change from baseline in body weight (kg) after 26 weeks
change from baseline in total daily insulin dose (TDID), U/kg, after 26 weeks
change from baseline in the percentage of time spent in target glucose range of
70-180 mg/dL (3.9-10.0 mmol/L) as determined by continuous glucose
monitoring (CGM) in weeks 23 to 26
change from baseline in systolic blood pressure (SBP) after 26 weeks
change from baseline in diastolic blood pressure (DBP) after 26 weeks
Inclution Criteria
Inclusion criteria
1. Signed and dated written informed consent by the date of Visit 1 in accordance with
Good Clinical Practice (GCP) and local legislation
2. Male or female patient receiving insulin for the treatment of documented diagnosis of
T1DM for at least 1 year at the time of Visit 1
3. Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central
laboratory
4. Use of, and be willing, based on the Investigator’s judgement, to continue throughout the
duration of the trial, either:
MDI of insulin consisting of at least one basal insulin injection and at least three daily
bolus injections OR
CSII of any insulin type, with at least 5 months experience of using CSII prior to Visit
1
For both MDI and CSII, the total daily insulin dose must be ≥ 0.3 U/kg and ≤ 1.5 U/kg at
Visit 1
5. HbA1c ≥ 7.5% and ≤ 10.0% at Visit 5 measured by the central laboratory, and provided
that the patient’s HbA1c does not increase by > 0.3% between Visit 1 and Visit 5
6. Based on the Investigator’s judgement patient must have a good understanding of his/her
disease and how to manage it, and be willing and capable of performing the following
study assessments (assessed at Visits 1-5 and just before randomisation):
patient-led management and adjustment of insulin therapy
reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
reliable and regular home-based blood glucose monitoring
recognise the symptoms of DKA, and reliably monitor for ketones
implementation of an established “sick day” management regimen
7. Age ≥ 18 years at Visit 1
8. Body Mass Index (BMI) of ≥ 18.5 kg/m2
at Visit 1
9. eGFR ≥ 30 mL/min/1.73 m² as calculated by the CKD-EPI formula, based on creatinine
measured by the central laboratory at Visit 1
10. Women of child-bearing potential* must be ready and able to use highly effective
methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1%
per year when used consistently and correctly. Such methods should be used throughout
the study and the patient must agree to periodic pregnancy testing during participation in
the trial. A list of contraceptive methods meeting these criteria will be provided in the
patient information
*Women of child-bearing potential are defined as follows:
Any female who has experienced menarche and is not post-menopausal (defined as at
least 12 months with no menses without an alternative medical cause) or who is not
permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral oophorectomy or
bilateral salpingectomy)
11. Compliance with trial medication administration must be between 80% and 120% during
the open-label placebo run-in period (see Section 4.1.8.1 for calculation of compliance),
to be judged before randomisation
1. Signed and dated written informed consent by the date of Visit 1 in accordance with
Good Clinical Practice (GCP) and local legislation
2. Male or female patient receiving insulin for the treatment of documented diagnosis of
T1DM for at least 1 year at the time of Visit 1
3. Fasting C-peptide value of < 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central
laboratory
4. Use of, and be willing, based on the Investigator’s judgement, to continue throughout the
duration of the trial, either:
MDI of insulin consisting of at least one basal insulin injection and at least three daily
bolus injections OR
CSII of any insulin type, with at least 5 months experience of using CSII prior to Visit
1
For both MDI and CSII, the total daily insulin dose must be ≥ 0.3 U/kg and ≤ 1.5 U/kg at
Visit 1
5. HbA1c ≥ 7.5% and ≤ 10.0% at Visit 5 measured by the central laboratory, and provided
that the patient’s HbA1c does not increase by > 0.3% between Visit 1 and Visit 5
6. Based on the Investigator’s judgement patient must have a good understanding of his/her
disease and how to manage it, and be willing and capable of performing the following
study assessments (assessed at Visits 1-5 and just before randomisation):
patient-led management and adjustment of insulin therapy
reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
reliable and regular home-based blood glucose monitoring
recognise the symptoms of DKA, and reliably monitor for ketones
implementation of an established “sick day” management regimen
7. Age ≥ 18 years at Visit 1
8. Body Mass Index (BMI) of ≥ 18.5 kg/m2
at Visit 1
9. eGFR ≥ 30 mL/min/1.73 m² as calculated by the CKD-EPI formula, based on creatinine
measured by the central laboratory at Visit 1
10. Women of child-bearing potential* must be ready and able to use highly effective
methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1%
per year when used consistently and correctly. Such methods should be used throughout
the study and the patient must agree to periodic pregnancy testing during participation in
the trial. A list of contraceptive methods meeting these criteria will be provided in the
patient information
*Women of child-bearing potential are defined as follows:
Any female who has experienced menarche and is not post-menopausal (defined as at
least 12 months with no menses without an alternative medical cause) or who is not
permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral oophorectomy or
bilateral salpingectomy)
11. Compliance with trial medication administration must be between 80% and 120% during
the open-label placebo run-in period (see Section 4.1.8.1 for calculation of compliance),
to be judged before randomisation
Exclusion Criteria
Exclusion criteria
1. History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or
chronic pancreatitis
2. Pancreas, pancreatic islet cells or renal transplant recipient
3. T1DM treatment with any other antihyperglycaemic drug (e.g. metformin, alphaglucosidase inhibitors, glucagon-like-peptide 1 (GLP-1) analogues, SGLT-2 inhibitors,
pramlintide, inhaled insulin, pre-mixed insulins etc.) except subcutaneous basal and bolus
insulin within 3 months prior to Visit 1 or any history of clinically relevant
hypersensitivity according to Investigator’s judgement
4. Occurrence of severe hypoglycaemia involving coma and/or seizure that required
hospitalisation or hypoglycaemia-related treatment by an emergency physician or
paramedic within 3 months prior to Visit 1
5. Occurrence of severe DKA (i.e. a pH of < 7.0 or prolonged Intensive Care Unit [ICU]
admission exceeding two days) requiring hospitalisation within 3 months prior to Visit 1
6. Irregular sleep/wake cycle (e.g. patients who habitually sleep during the day and work
during the night) based on Investigator’s judgement
7. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or
transient ischaemic attack (TIA) within 3 months prior to Visit 1
8. Diagnosis of severe gastroparesis (based on Investigator’s judgement)
9. Diagnosis of brittle diabetes based on Investigator judgement
10. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT),
aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal
(ULN) at Visit 1 or Visit 5 as measured by the central laboratory
11. Eating disorders such as bulimia or anorexia nervosa
12. Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen leading
to unstable body weight (based on Investigator’s judgement) 3 months prior to Visit 1
and until randomisation
13. Treatment with systemic corticosteroids or planned initiation of such therapy at Visit 1.
Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary
disease) is acceptable
14. Change in dose of thyroid hormones within 6 weeks prior to Visit 1 or planned change or
initiation of such a therapy at Visit 1
15. Patient must be willing, based on the Investigator’s judgement, not to take any
paracetamol (acetaminophen) containing drugs throughout the CGM monitoring periods,
since this may falsely raise CGM glucose readings
16. Medical history of cancer or treatment for cancer in the last five years prior to Visit 1.
Resected basal cell carcinoma considered cured is exempted
17. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g.
malaria, babesiosis, haemolytic anaemia) at Visit 1
18. Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial
19. Alcohol or drug abuse within the 3 months prior to Visit 1 that would interfere with trial
participation based on Investigator’s judgement
20. Intake of an investigational drug in another trial within 30 days prior to Visit 1
21. Patient not able to understand and comply with study requirements, including the use of
an e-diary, based on Investigator’s judgement
22. Any other clinical condition that, based on Investigator’s judgement, would jeopardise
patient safety during trial participation or would affect the study outcome (e.g.
immunocompromised patients who might be at higher risk of developing genital or
mycotic infections, patients with chronic viral infections etc.)
1. History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or
chronic pancreatitis
2. Pancreas, pancreatic islet cells or renal transplant recipient
3. T1DM treatment with any other antihyperglycaemic drug (e.g. metformin, alphaglucosidase inhibitors, glucagon-like-peptide 1 (GLP-1) analogues, SGLT-2 inhibitors,
pramlintide, inhaled insulin, pre-mixed insulins etc.) except subcutaneous basal and bolus
insulin within 3 months prior to Visit 1 or any history of clinically relevant
hypersensitivity according to Investigator’s judgement
4. Occurrence of severe hypoglycaemia involving coma and/or seizure that required
hospitalisation or hypoglycaemia-related treatment by an emergency physician or
paramedic within 3 months prior to Visit 1
5. Occurrence of severe DKA (i.e. a pH of < 7.0 or prolonged Intensive Care Unit [ICU]
admission exceeding two days) requiring hospitalisation within 3 months prior to Visit 1
6. Irregular sleep/wake cycle (e.g. patients who habitually sleep during the day and work
during the night) based on Investigator’s judgement
7. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or
transient ischaemic attack (TIA) within 3 months prior to Visit 1
8. Diagnosis of severe gastroparesis (based on Investigator’s judgement)
9. Diagnosis of brittle diabetes based on Investigator judgement
10. Indication of liver disease, defined by serum levels of either alanine transaminase (ALT),
aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal
(ULN) at Visit 1 or Visit 5 as measured by the central laboratory
11. Eating disorders such as bulimia or anorexia nervosa
12. Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen leading
to unstable body weight (based on Investigator’s judgement) 3 months prior to Visit 1
and until randomisation
13. Treatment with systemic corticosteroids or planned initiation of such therapy at Visit 1.
Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary
disease) is acceptable
14. Change in dose of thyroid hormones within 6 weeks prior to Visit 1 or planned change or
initiation of such a therapy at Visit 1
15. Patient must be willing, based on the Investigator’s judgement, not to take any
paracetamol (acetaminophen) containing drugs throughout the CGM monitoring periods,
since this may falsely raise CGM glucose readings
16. Medical history of cancer or treatment for cancer in the last five years prior to Visit 1.
Resected basal cell carcinoma considered cured is exempted
17. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g.
malaria, babesiosis, haemolytic anaemia) at Visit 1
18. Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial
19. Alcohol or drug abuse within the 3 months prior to Visit 1 that would interfere with trial
participation based on Investigator’s judgement
20. Intake of an investigational drug in another trial within 30 days prior to Visit 1
21. Patient not able to understand and comply with study requirements, including the use of
an e-diary, based on Investigator’s judgement
22. Any other clinical condition that, based on Investigator’s judgement, would jeopardise
patient safety during trial participation or would affect the study outcome (e.g.
immunocompromised patients who might be at higher risk of developing genital or
mycotic infections, patients with chronic viral infections etc.)
The Estimated Number of Participants
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Taiwan
35 participants
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Global
720 participants
